title: Darbepoetin alfa for anemia in patients with low or intermediate-1 risk myelodysplastic syndromes and positive predictive factors of response.
abstract: BACKGROUND
  Current guidelines support the use of erythropoiesis-stimulating agents for the treatment of anemia associated with low-risk myelodysplastic syndromes (MDS).
  
  
  METHODS
  Single-arm, open-label, multi-center, phase 2 trial that evaluated the efficacy and safety of darbepoetin alfa (DA) in patients with low or intermediate-risk MDS, hemoglobin <100 g/L, erythropoietin (EPO) levels <500 IU/L and transfusion requirements <2 units/month over the preceding 2 months. Erythroid response (major [MaR] or minor [MiR]) and fatigue (Functional Assessment of Cancer Therapy-Fatigue [FACT-F]) were evaluated at 8, 16 and 24 weeks. DA was initiated at 300 μg weekly. For patients who did not achieve MaR by 8 weeks, filgrastim 300 μg weekly was added.
  
  
  BACKGROUND
  clinicaltrials.gov identifier: NCT01039350.
  
  
  RESULTS
  Forty-four patients (72.7% transfusion independent) were included. Median age was 76.0 years (range 41.3-92.4), 54.5% were male, and 90.9% presented ECOG Status (0-1). Eighteen patients received filgrastim. An erythroid response was achieved by 31 of 44 patients (70.5%) at week 8 (47.7% MaR, 22.7% MiR), 31 of 44 patients (70.5%) at week 16 (61.4% MaR, 9.1% MiR), and 32 of 44 patients (72.7%) at week 24 (61.3% MaR, 11.4% MiR). Mean (95% CI) change in FACT-F at week 24 was 3.61 (0.72 to 6.51). Baseline EPO levels <100 IU/L were a predictive factor of response. DA was well tolerated. Four mild (two iron deficiencies, flu syndrome and headache) and one fatal (thromboembolic event) adverse events were considered related to darbepoetin alfa.
  
  
  CONCLUSIONS
  A fixed dose of 300 μg of darbepoetin alfa weekly (with or without filgrastim) seems to be an effective and safe treatment for anemic patients with low or intermediate-risk MDS, low transfusion burden and EPO levels <500 IU/L. Results may not be extrapolable to unselected MDS patients.
authors.affiliation: Hematology Department, Hospital Clínico San Carlos Universidad Complutense, Madrid, Spain. avillegas.hcsc@salud.madrid.org
authors.forename: A
authors.initials: A
authors.lastname: Villegas
authors.forename: B
authors.initials: B
authors.lastname: Arrizabalaga
authors.forename: C
authors.initials: C
authors.lastname: Fernández-Lago
authors.forename: M
authors.initials: M
authors.lastname: Castro
authors.forename: J R
authors.initials: JR
authors.lastname: Mayans
authors.forename: J R
authors.initials: JR
authors.lastname: González-Porras
authors.forename: R F
authors.initials: RF
authors.lastname: Duarte
authors.forename: A F
authors.initials: AF
authors.lastname: Remacha
authors.forename: E
authors.initials: E
authors.lastname: Luño
authors.forename: J A
authors.initials: JA
authors.lastname: Gasquet
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects; D006454:Hemoglobins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D012307:Risk Factors
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa